We will continue our studies of the behavior of murine hematopoietic cells modified by acquired drug-resistance genes. We have recently cloned the gene for a mutant dihydrofolate reductase (DHFR) that is enzymatically active but highly resistant to inhibition by methotrexate (MTX) and certain other folic acid antagonists. We wish to test the effectiveness of the cloned gene in transforming mouse bone marrow cells to a state of MTX resistance. We plan to examine alternative strategies for modulating the transcription of the inserted drug-resistance gene sequences so that gene expression can be modified by the imposition of compounds such as glucocorticoids.